Orgaran® use in intensive care unit patients with heparin-induced thrombocytopenia and acute renal failure
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KeywordsInfusion Rate Orgaran Continuous Renal Replacement Therapy Disseminate Intravascular Coagulation Multiple Organ Dysfunction Syndrome
Orgaran® (danaparoid sodium) is a low-molecular-weight, nonheparin glycosaminoglycan antithrombotic that is currently a first-line treatment for heparin-induced thrombocytopenia (HIT). This study reports on the safety of Orgaran® in ICU patients suffering from HIT and acute renal failure requiring continuous renal replacement therapy (haemofiltration).
Data on 96 case reports from personal experience and publications have been collated.
Nineteen females and 59 males (18 unknown gender) with a median age of 60 years (range 22–95 years) presented with a variety of clinical problems that either preceded or complicated their HIT; for example, postoperative/accidental trauma or overt bleeding in 61, sepsis/septicaemia/septic shock in 37, thromboembolism in 23, multiple organ dysfunction syndrome in 14, disseminated intravascular coagulation in eight and other miscellaneous serious problems in 38.
A variety of continuous extracorporeal haemofiltration circuits was used for from 1 to 39 days (median 7 days). The Orgaran® dosing schedule was usually initiated with a 2,000–2,500 U intravenous bolus injection. After two step-down dose periods the subsequent maintenance infusion was usually titrated according to each patient's thromboembolic and bleeding risk status. Hence most patients received 100–400 U/hour, but 11 patients required up to 600 U/hour temporarily to control extracorporeal circuit clotting.
There were 12 minor bleeding events, occurring mostly during the maintenance infusion rate adjustment period and which responded to transient interruption and/or lowering of the infusion rate. Eleven nonfatal major bleeding events occurred (four due to procedural errors) and eight fatal major bleeds, two of which occurred 3 days and 8 days after Orgaran® discontinuation.
Plasma anti-FXa levels were reported for 38 patients. During seven of the eight fatal bleeding episodes the plasma anti-FXa levels were ≥0.8 U/ml in three patients and 0.31–0.66 U/ml (that is, within the target range) in the other four patients. The highest anti-FXa response of 2.00 U/ml was associated with minor bleeding from an angiomatous malformation and stopped when the Orgaran® dose was reduced. However, of the 11 patients receiving >400 U/hour, four suffered major bleeding (three fatal) and two developed minor bleeding. Most of these patients received continuous arterio-venous haemodiafiltration treatment, which may have been a contributory factor.
We recommend that maintenance Orgaran® infusion rates ≥400 U/hour should be avoided unless serious circuit clotting is grossly affecting the haemofilter life. The infusion rate should be monitored clinically; that is, on the basis of bleeding and circuit clotting rather than the patients' plasma anti-FXa responses.